DESCRIPTION: Progress is being made in developing neuroprotective strategies for traumatic brain injuries; however, there will never be a therapy that will fully preserve neurons that are injured from moderate to severe head injuries. Therefore, to restore neurological function, regenerative strategies will be required. Despite significant progress in stem cell transplantation after TBI, problems exist that limit the utility of these cells; namely the source of stem cells, teir homogeneity and transplantation techniques. The goal of this project is to test the hypothesis that a novel multifunctional scaffold that we have developed as a platform for transplanting primitive neural precursors, will improve engraftment and promote regeneration of neocortical brain cells after a focal brain injury. Without a matrix the cells lack a physical as well as a trohic substrate and thus the vast majority dies. With this application we propose to continue the studies reported in our preliminary data using rat VZ cells. However, the major goal of this application is to move our work closer to clinical applications. Our specific aims are: 1) To test the hypothesis that a multifunctional scaffold will improve the engraftment of primitive neural precursors in an adult brain traumatic injury animal model; and 2) To evaluate the engraftment of human NPs in an adult rat brain injury animal model. In addition to assessing the extent of engraftment and the types of neurons and glial cells formed as well as their laminar topology, we will assess the functional properties of the regenerated neurons using state of the art electrophysiological recordings and we will evaluate sensorimotor behavior to test for improvements in neurological function. Moreover, we will genetically engineer the human neural precursors to be transplanted so that we can eliminate the engrafted cells and then re-evaluate their neurological function to establish whether the engrafted cells are truly essential for the recovery of function obtained. Upon completing the research proposed here the efficacy of a new platform will have been tested for regenerative medicine as applied to neopallial traumatic brain injuries.